The recent development of prophylactic cervical cancer vaccines is a significant achievement in cancer prevention. The two currently available vaccines are composed of recombinant virus- like particles (VLPs) of the major viral capsid protein for the HPV types 16 and 18, the most common high-risk types in North America and Europe. These VLP vaccines prevent infection and intermediate stage lesions caused by HPV 16 and 18. Thus, the vaccine hopefully will prevent the development of about 70% of cervical cancers associated with these HPV types. Despite this success, VLP vaccines have several detrimental characteristics including lack of protection against other HPV types, their high cost ($360 for the initial three immunizations in the USA) and a requirement for refrigeration (i.e., cold chain). We have shown that VLP subunits, pentameric L1 capsomeres, appear nearly equivalent to VLPs in inducing protection against infection in animal models. These capsomeres can be purified after recombinant expression of GST-L1 fusion proteins in E. coli, which will significantly reduce manufacturing expense. The recombinant GST-L1 protein is readily purified, and can be precipitated, resuspended, and stored at room temperature without loss of immunogenicity. This proposal aims to show that multivalent combinations of capsomere vaccines can elicit type-specific neutralizing antibodies against a variety of high-risk HPV virus types, including those prevalent in the developing world. PUBLIC HEALTH RELEVANCE: It is estimated that one woman dies of cervical cancer every 2 minutes in resource-poor countries and most cases of cervical cancer are caused by infection with one of several types of human papilloma virus (HPV). Thus, there is an urgent public health need for a low-cost cervical cancer vaccine that is accessible to underdeveloped areas of the world and protects against multiple cancer-causing HPV viruses. The goal of this project is to develop multivalent "capsomere"-based HPV vaccines that can be manufactured at a cost affordable to all. [unreadable] [unreadable] [unreadable]